Dystonis in ataxia telangiectasia: Report of a case with putaminal lesions and decreased striatal [¹²³I]Iodobenzamide Binding

Abstract

A 6-year-old girl with ataxia telangiectasia and severe progressive dystonic posturing is presented. Magnetic resonance imaging showed cerebellar atrophy and a right-sided putaminal lesion. A single-photon emission computed tomography study of cerebral dopamine-(D2)-receptor binding with [123I]iodobenzamide showed a decreased tracer uptake in the striatum bilaterally. Dystonia deteriorated with levodopa treatment, whereas trihexyphenidyl led to significant improvement. Although dystonic symptoms have been repeatedly described in ataxia telangiectasia, this is the first report demonstrating structural and functional basal ganglia abnormalities in this disorder.

Loss of Neuronal Cell Cycle Control in Ataxia-Telangiectasia: A Unified Disease Mechanism

“…Pathological examination reveals significant degeneration of cerebellar Purkinje and granule cells (Crawford, 1998) plus a later loss of neurons in striatum and substantia nigra (Ostetowska and Traczynska, 1964;Koepp et al, 1994). The disease is associated with mutations in ataxiatelangiectasia mutated (ATM), a gene encoding a 370 kDa serine/ threonine kinase with sequence similarity to the catalytic subunit of phosphatidyl-inositol-3-kinase (Savitsky et al, 1995).…”

Nucleocytoplasmic Cdk5 is involved in neuronal cell cycle and death in post-mitotic neurons

“…Even ataxia-telangiectasia (A-T), which strikes most often in childhood can present in the adult and when it does, the degeneration is most profound in cerebellar Purkinje and granule cells 5 with a later loss of neurons in striatum and substantia nigra. 6,7 In each of these cases, while we have learned much about the biochemistry that accompanies the degeneration, in most situations this chemistry is shared by neurons across the CNS, making the anatomical specificity of the disease difficult to understand.…”

DNA-damage response, survival and differentiation in vitro of a human neural stem cell line in relation to ATM expression

“…3 The occurrence of ataxia, which typically appears in infancy, reflects the progressive degeneration of the cerebellar cortex due to the loss of Purkinje and granule cells. 4,5 Loss of neurons in striatum and substantia nigra are also observed in A-T. 6 A-T results from inactivating mutations in A-T mutated (ATM) gene coding for a kinase with an essential role in responding and transducing the signal arising from DNA double-strand breaks (DSBs). 7 ATM, along with the MRN (Mre11-Rad50-Nbs1) complex senses DSBs, leading to ATM autophosphorylation on serine 1981, and phosphorylation of a plethora of substrates involved in cell-cycle checkpoint arrest, repair of breaks, chromatin remodeling and cell death.…”